The objectives of this work are (1) to determine the biochemical function of alkaline phosphatase in the cell membrane, and (2) to determine the significance of this function in leukemogenesis and the normal immune response. This enzyme appears in the fetal thymus only up to sixteen days gestation in C57BL mice and then reappears in the thymic lymphoma. Biochemical characterization of this isozyme shows it to be similar to the alkaline phosphatase found in the placenta and in the cells surrounding the perivascular lymphatic sheath in the spleen of C57BL mice. It is suggested that this enzyme may represent a fetal function which is present in the placenta, in the thymus up to sixteen days gestation, in spleen cells undergoing blast transformation, and in leukemic lymphoblasts. Alkaline phosphatase will be purified from the thymic lymphoma, placenta and adult spleen and mechanistic studies performed on these purified enzymes to determine the biochemical function. Suggested functions include active transport of ions, active transport of nutrients, and protein kinase activity in cyclic AMP-related cell membrane functions. Experiments are outlined to support or refute these hypotheses. In order to determine the significance of the alkaline phosphatase activity in the normal immune response and leukemogenesis, the cells of the normal spleen, fetal thymus and preleukemic bone marrow will be tested for their alkaline phosphatase, theta antigen, H-2 antigen, TL antigen, and immunoglobulin content. Cell and organ culture systems will be used to determine the mechanism of induction of alkaline phosphatase in both the normal immune response and leukemogenesis. Since alkaline phosphatase is a membrane-bound activity, the proposed work will contribute to the understanding of the controls involved in leukemogenesis and the normal immune response by providing information concerning cell membrane function in the control of cellular proliferation. BIBLIOGRAPHIC REFERENCE: Lumb, J.R. and Y.S. George. 1976. Serum-free cultivation of thymus organ fragments. Fed. Proc. 35, 2555-2558.